Non-alcoholic Steatohepatitis
Conditions
Brief summary
This study will evaluate the efficacy, safety, and pharmacokinetics of BFKB8488A compared to placebo in participants with non-alcoholic steatohepatitis (NASH).
Interventions
DRUGPlacebo
Participants will receive subcutaneous (SC) placebo matched to BFKB8488A.
DRUGBFKB8488A
Participants will receive subcutaneous (SC) BFKB8488A.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of NASH as documented through liver biopsy performed no more than 6 months before randomization, defined according to NASH CRN criteria along with a NASH CRN fibrosis score between F2 and F3 * Hepatic steatosis on MRI (\>= 8% average PDFF) prior to randomization
Exclusion criteria
* History of any liver disease other than NASH, except for resolved, self-limited illnesses such as Hepatitis A or E, and previous Hepatitis C * Weight gain \> 10% or loss \> 5% within 3 months prior to randomization * History of liver transplantation * Current or history of significant alcohol consumption
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52 | Week 52 | Resolution of non-alcoholic steatohepatitis (NASH) is defined as a non-alcoholic fatty liver disease activity score (NAS) of 0-1 for inflammation, 0 for ballooning, and any value for steatosis as determined by a central reader. Worsening of fibrosis is defined as any increase in NASH Clinical Research Network (CRN) fibrosis stage as determined by a central reader. |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Participants With Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52 | Week 52 |
| Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Baseline, Week 16, Week 52 |
| Proportion of Participants With Improvement in Liver Histology From Baseline and no Worsening of Fibrosis at Week 52 | Week 52 |
Countries
Belgium, France, Puerto Rico, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo by subcutaneous (SC) injection every two weeks (Q2W) for 52 weeks. | 13 |
| Fixed Dose 50 mg Participants received 50 mg of SC fazpilodemab (BFKB8488A) Q2W for 52 weeks. | 11 |
| Fixed Dose 75 mg Participants received 75 mg of SC fazpilodemab (BFKB8488A) Q2W for 52 weeks. | 11 |
| Fixed Dose 100 mg Participants received 100 mg of SC fazpilodemab (BFKB8488A) Q2W for 52 weeks. | 11 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 2 | 2 |
| Overall Study | Study terminated by sponsor | 2 | 0 | 0 | 0 |
| Overall Study | Week 58 visit missed | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | Fixed Dose 50 mg | Fixed Dose 75 mg | Fixed Dose 100 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.4 Years STANDARD_DEVIATION 9.6 | 57.4 Years STANDARD_DEVIATION 10 | 55.4 Years STANDARD_DEVIATION 8.2 | 51.9 Years STANDARD_DEVIATION 14.8 | 53.0 Years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 3 Participants | 5 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 10 Participants | 9 Participants | 10 Participants | 42 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 5 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 9 / 13 | 11 / 11 | 9 / 11 | 10 / 11 |
| serious Total, serious adverse events | 0 / 13 | 1 / 11 | 1 / 11 | 0 / 11 |
Outcome results
Primary
Proportion of Participants With NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52
Resolution of non-alcoholic steatohepatitis (NASH) is defined as a non-alcoholic fatty liver disease activity score (NAS) of 0-1 for inflammation, 0 for ballooning, and any value for steatosis as determined by a central reader. Worsening of fibrosis is defined as any increase in NASH Clinical Research Network (CRN) fibrosis stage as determined by a central reader.
Time frame: Week 52
Population: The modified intent-to-treat (mITT) population was defined as all randomly allocated participants who received at least one dose of study drug or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52 | 16.7 Percentage of Participants |
| Fixed Dose 50 mg | Proportion of Participants With NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52 | 37.5 Percentage of Participants |
| Fixed Dose 75 mg | Proportion of Participants With NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52 | 14.3 Percentage of Participants |
| Fixed Dose 100 mg | Proportion of Participants With NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52 | 33.3 Percentage of Participants |
Secondary
Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52
Time frame: Baseline, Week 16, Week 52
Population: The mITT population was defined as all randomly allocated participants who received at least one dose of study drug or placebo.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 52 change from baseline | -4.46 percentage of hepatic fat fraction | Standard Deviation 6.23 |
| Placebo | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Baseline | 20.15 percentage of hepatic fat fraction | Standard Deviation 6.35 |
| Placebo | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 16 change from baseline | -3.47 percentage of hepatic fat fraction | Standard Deviation 2.28 |
| Fixed Dose 50 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 16 change from baseline | -8.20 percentage of hepatic fat fraction | Standard Deviation 8.58 |
| Fixed Dose 50 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Baseline | 20.67 percentage of hepatic fat fraction | Standard Deviation 6.05 |
| Fixed Dose 50 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 52 change from baseline | -2.50 percentage of hepatic fat fraction | Standard Deviation 8.13 |
| Fixed Dose 75 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 52 change from baseline | -3.46 percentage of hepatic fat fraction | Standard Deviation 11.57 |
| Fixed Dose 75 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Baseline | 19.30 percentage of hepatic fat fraction | Standard Deviation 3.99 |
| Fixed Dose 75 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 16 change from baseline | -2.23 percentage of hepatic fat fraction | Standard Deviation 9.05 |
| Fixed Dose 100 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 16 change from baseline | -10.25 percentage of hepatic fat fraction | Standard Deviation 4.76 |
| Fixed Dose 100 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Baseline | 18.12 percentage of hepatic fat fraction | Standard Deviation 7.7 |
| Fixed Dose 100 mg | Change From Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 | Week 52 change from baseline | -3.53 percentage of hepatic fat fraction | Standard Deviation 6.54 |
Secondary
Proportion of Participants With Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52
Time frame: Week 52
Population: The mITT population was defined as all randomly allocated participants who received at least one dose of study drug or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52 | 16.7 Percentage of participants |
| Fixed Dose 50 mg | Proportion of Participants With Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52 | 25.0 Percentage of participants |
| Fixed Dose 75 mg | Proportion of Participants With Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52 | 28.6 Percentage of participants |
| Fixed Dose 100 mg | Proportion of Participants With Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52 | 16.7 Percentage of participants |
Secondary
Proportion of Participants With Improvement in Liver Histology From Baseline and no Worsening of Fibrosis at Week 52
Time frame: Week 52
Population: The mITT population was defined as all randomly allocated participants who received at least one dose of study drug or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With Improvement in Liver Histology From Baseline and no Worsening of Fibrosis at Week 52 | 16.7 Percentage of participants |
| Fixed Dose 50 mg | Proportion of Participants With Improvement in Liver Histology From Baseline and no Worsening of Fibrosis at Week 52 | 37.5 Percentage of participants |
| Fixed Dose 75 mg | Proportion of Participants With Improvement in Liver Histology From Baseline and no Worsening of Fibrosis at Week 52 | 42.9 Percentage of participants |
| Fixed Dose 100 mg | Proportion of Participants With Improvement in Liver Histology From Baseline and no Worsening of Fibrosis at Week 52 | 33.3 Percentage of participants |